scholarly journals Evaluation of Synergistic Effect of Cytosine-Phosphodiesterbond-Guanosin-Oligodeoxynucleotide 7909, and Protamine on Transfection Process Mediated by Calcium Phosphate Nanoparticles

2020 ◽  
Vol 10 (01) ◽  
pp. 52-59
Author(s):  
Ghassaq T. Al-Ubaidi ◽  
Ahmed A. Abbas ◽  
Ali A. Taha ◽  
Qasim S. Sharhan ◽  
Israa W. Ahmed ◽  
...  

Bacille Calmette-Guerin (BCG) still the only authenticated vaccine against tuberculosis. Due to its drawbacks, a need for a new formula has emerged. The implication of “Nanovaccinology” is one of the possible alternatives. The non-viral vectors have a low transfection ability. In the context, this work aims to add two adjuvants to a calcium phosphate nanoparticles (CPNPs) functionalized with early secreted antigenic target 6-kilo dalton ( ESAT-6) cloned pcDNA3.1(+) plasmid. ESAT-6 gene is specific to mycobacterium tuberculosis complex (MTC) and encodes a T-cell antigen. The adjuvants in practice are Herring protamine and cytosine-phosphodiester bond-guanosine-oligodeoxynucleotide 7909 ( CpG-ODN 7909). Each has a different strategy in enhancing immune response; protamine is particulate adjuvant while CpG is an immunopotentiator substance. Nano complex was transfected into THP-1 monocytic cell line after its activation to a macrophage via 100nM PMA. Cellular immune response, interleukin-12 (IL-12), and tumor necrosis factor –alfa (TNF-ɑ) also ESAT-6 protein production were assayed via the Sandwich ELISA technique. Results revealed that CPNPs offer only partial protection to the adsorbed plasmid against enzymatic degradation. Nano complex formula with two adjuvants resulted in significantly higher cellular immune response comparing to formula carrying one adjuvant. In conclusion, the implication of CPNPs in gene delivery accompanied with two adjuvants each possess different strategy, will result in partial protection to the delivered gene with upsurge cellular immune response.

2008 ◽  
Vol 15 (8) ◽  
pp. 1229-1237 ◽  
Author(s):  
Evelyn Guirado ◽  
Olga Gil ◽  
Neus Cáceres ◽  
Mahavir Singh ◽  
Cristina Vilaplana ◽  
...  

ABSTRACT RUTI is a therapeutic vaccine that is generated from detoxified and liposomed Mycobacterium tuberculosis cell fragments that has demonstrated its efficacy in the control of bacillus reactivation after short-term chemotherapy. The aim of this study was to characterize the cellular immune response generated after the therapeutic administration of RUTI and to corroborate the lack of toxicity of the vaccine. Mouse and guinea pig experimental models were infected with a low-dose M. tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in both experimental models. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mouse and guinea pig models. This was not the case after Mycobacterium bovis BCG treatment. Cellular immunity was studied through the characterization of the intracellular gamma interferon (IFN-γ)-producing cells after the splenocytes' stimulation with M. tuberculosis-specific structural and growth-related antigens. Our data show that the difference between the therapeutic administration of BCG and RUTI resides mainly in the stronger activation of IFN-γ + CD4+ cells and CD8+ cells against tuberculin purified protein derivative, ESAT-6, and Ag85B that RUTI generates. Both vaccines also triggered a specific immune response against the M. tuberculosis structural antigens Ag16kDa and Ag38kDa and a marked mRNA expression of IFN-γ, tumor necrosis factor, interleukin-12, inducible nitric oxide synthase, and RANTES in the lung. The results show that RUTI's therapeutic effect is linked not only to the induction of a Th1 response but also to the stimulation of a quicker and stronger specific immunity against structural and growth-related antigens that reduces both the bacillary load and the pulmonary pathology.


1999 ◽  
Vol 37 (2) ◽  
pp. 123-129 ◽  
Author(s):  
B. R. Mignon ◽  
T. Leclipteux ◽  
CH. Focant ◽  
A. J. Nikkels ◽  
G. E. PIErard ◽  
...  

2004 ◽  
Vol 146 (4) ◽  
pp. 159-172 ◽  
Author(s):  
D. Müller-Doblies ◽  
S. Baumann ◽  
P. Grob ◽  
A. Hülsmeier ◽  
U. Müller-Doblies ◽  
...  

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 180-184 ◽  
Author(s):  
György T. Szeifert ◽  
Isabelle Salmon ◽  
Sandrine Rorive ◽  
Nicolas Massager ◽  
Daniel Devriendt ◽  
...  

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.


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